The mechanisms by which various classes of chemical stimuli are detected and how that translates into appropriate behaviors is a central problem in gustatory neurobiology. The overarching objective of this proposal is to investigate the molecular and cellular mechanisms of carboxylic acid taste in Drosophila, and to identify neurophysiological responses to carboxylic acids in the mosquito, Aedes aegypti. Drosophila is an excellent model to study the fundamental logic by which the taste system is organized in insects. While a lot of progress has been made in deciphering the molecular and cellular mechanisms of certain categories of tastants including sweet and bitter compounds, little is known about the fly's taste responses to acids. Based on preliminary studies, the central hypothesis of this proposal is that acid stimuli can activate and inhibit different categories of taste neurons, and acid-mediated inhibition of taste neurons is dependent on the function of a highly conserved member of the Ionotropic receptor family, Ir25a. The approach to test this hypothesis will be to: 1) undertake electrophysiological analyses to characterize activation of taste neurons by carboxylic acids, 2) validate the identity of taste neurons that are activated in response to acid stimuli and determine their contribution in acid aversion behavior, 3) characterize acid-mediated inhibition of sweet neurons, 4) link the function of Ir25a to acid-mediated inhibition of sugar neurons, and 5) initiate an analysis of excitatory and inhibitory responses to acids in taste neurons of Aedes aegypti. The proposed research is innovative because it represents a departure from previous studies of chemosensory responses to carboxylic acids that focused on the role of the olfactory system, and because the research plan encompasses a multidisciplinary approach spanning genetic, electrophysiological and behavioral analyses. The proposed research is significant because it will provide insight into the molecular and cellular basis of acid taste in a valuable model organism, which will aid in studying fundamental problems of chemosensory coding and behavior. Notably, carboxylic acids of low volatility are components of human sweat and their detection by taste neurons may be important for behaviors of human blood-feeding insects such as Aedes aegypti and Anopheles gambiae, which transmit deadly diseases. An understanding of the function of evolutionarily conserved receptors in the detection of carboxylic acids may lead to novel strategies for control of arthropod disease vectors.